Within the past 24 months, Mycoplasma fermentans, strain incognitus, has been detected in tissues taken at autopsies from AIDS patients with respiratory, central nervous system (CNS), and renal disease. At the 1991 general meeting of the American Society for Microbiology, increased incidence of M. fermentans was shown in the urine of AIDS patients compared to age and sex-matched non-AIDS patients. In addition, M. fermentans and other mycoplasmas have been reported in the blood of AIDS patients. More recently mycoplasmas, especially M. fermentans strain incognitus, have even been proposed to be cofactors for HIV infection. In fact regulatory mechanisms of replication of human immunodeficiency virus (HIV) in vitro do suggest molecular mechanisms by which mycoplasmas could increase virus production in infected individuals. The mitogenic properties of mycoplasmas could increase HIV production in infected lymphocytes. Indeed other mitogens that act on T cells are known to enhance HIV production in vitro. Increased virus production is known to be associated with clinical progression in HIV-infected individuals. However, the incidence, natural history, pathogenic potential, and clinical significance of M.fermentans in AIDS patients is unknown. In addition, previous epidemiologic investigations have not yet demonstrated any clear association between progression of ADDS and any putative cofactor. Our long term goals are to determine if M. fermentans is either a cofactor in HIV infection or an important opportunistic pathogen. If M.fermentans is either, it then becomes important to determine the natural history of the infection. The specific aims of the present application are to: (i) identify sites of M.fermentans localization in autopsy tissues of AIDS patients and other patients with immunosuppression or other chronic debilitating diseases; (ii) identify HIV infected individuals who are co-infected with M. fermentans and identify matched controls who are HIV positive, M. fermentans negative; and (iii) determine if the rate of change in various parameters, including increase in HIV replication, decline in CD4+ lymphocytes or alterations in other lymphocyte subpopulations, and loss of immune responsiveness is greater in HIV-infected individuals with M. fermentans infection as compared to HIV-infected non-M.fermentans infected matched controls.